1. Field of the Invention
The invention relates to novel derivatives of mercaptopropionic acid and more particularly to esters with guaiacol (guaiacol esters) of alpha- and beta-mercaptopropionylalanine and of alpha- and beta-mercaptopropionylglycine, to the process for their preparation and to pharmaceutical compositions containing same.
The guaiacol esters of such mercaptopropionic acid derivatives are therapeutically useful as mucolytic agents.
2. Description of the Prior Art
To the best of the applicant's knowledge, the already known derivatives of mercaptopropionic acid more closely related to the compounds of the present invention are disclosed in the U.S. Pat. No. 3,246,025 the teachings of which are herein incorporated by reference.
The aforementioned patent discloses alpha- and beta-mercaptopropionylglycine, the amides and esters thereof, which are useful therapeutic agents for the treatment of drug intoxication and as antidotes in poisoning induced by mercury and arsenic compounds. In the preparation process as disclosed in the U.S. Patent, after having protected the sulfhydryl group of alpha- or beta-mercaptopropionic acid with an easily removable substituent in a successive reaction step, the carboxyl group is halogenated and the thus obtained acyl halide intermediate condensed with glycine to form the corresponding alpha- or beta-mercaptopropionylglycine derivative, from which the protective group is removed by conventional procedures. In order to obtain corresponding alpha- or beta-mercaptopropionylglycine amides or esters thereof, the acyl halide intermediate is made to react with either an already formed glycine amide or glycine ester respectively, instead of simply glycine.
The aforementioned U.S. Patent does not give any particular teachings regarding the nature of the protective substituents of the sulfhydryl group, the selection whereof is not evidently critical in view of the results to be accomplished, since it vaguely suggests that the sulfhydryl group is protected by a substituent that can easily be removed in a succeeding reaction, and confines the examples to benzyl, acetyl, nitrobenzyl and nitrobenzoyl. Also in regard to the removal of the protective group and the consequent recovery of the sulfhydryl the U.S. Patent does not disclose the specifically critical conditions it uses, ranging from the use of sodium metal in liquid ammonia (at approximately -50.degree. C.) to the use of concentrated ammonia, sodium hydroxide or barium hydroxide.